Fluorescence-in-situ-hybridization in the Surveillance of Urothelial Cancers: Can Use of Cystoscopy or Ureteroscopy be Deferred?

Ho, Christopher Chee Kong,Tan, Wei Phin,Pathmanathan, Rajadurai,Tan, Wei Keith,Tan, Hui Meng Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Background: Fluorescence in situ hybridization (FISH) testing may be useful to screen for bladder carcinoma or dysplasia by detecting aneuploidy chromosomes 3, 7, 17 and deletion of the chromosome 9p21 locus in urine specimens. This study aimed to assess the sensitivity, specificity, positive and negative predictive value of FISH in a multi-ethnic population in Asia. Materials and Methods: Patients with haematuria and/or past history of urothelial cancer on follow-up had their voided urine tested with FISH. Patients then underwent cystoscopy/ureteroscopy and any lesions seen were biopsied. The histopathological reports of the bladder or ureteroscopic mucosal biopsies were then compared with the FISH test results. Results: Two hundred sixty patients were recruited. The sensitivity and specificity of the FISH test was 89.2% and 83.4% respectively. The positive (PPV) and negative predictive values (NPV) were 47.1% and 97.9%. By excluding patients who had positive deletion of chromosome 9, the overall results of the screening test improved: sensitivity 84.6%; specificity 96.4%; PPV 75.9% and NPV 97.9%. Conclusions: UroVysion FISH has a high specificity of detecting urothelial cancer or dysplasia when deletion of chromosome 9 is excluded. Negative UroVysion FISH-tests may allow us to conserve health resources and minimize trauma by deferring cystoscopic or ureteroscopic examination.

Retrospective Study of Predictors of Bone Metastasis in Prostate Cancer Cases

Ho, Christopher Chee Kong,Seong, Poh Keat,Zainuddin, Zulkifli Md,Abdul Manaf, Mohd Rizal,Parameswaran, Muhilan,Razack, Azad H.A. Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5

Introduction: The purpose of this study was to identify clinical profiles of patients with low risk of having bone metastases, for which bone scanning could be safely eliminated. Materials and Methods: This retrospective cross sectional study looked at prostate cancer patients seen in the Urology Departments in 2 tertiary centres over the 11 year period starting from January 2000 to May 2011. Patient demographic data, levels of PSA at diagnosis, Gleason score for the biopsy core, T-staging as well as the lymph node status were recorded and analysed. Results: 258 men were included. The mean age of those 90 men (34.9%) with bone metastasis was $69.2{\pm}7.3$ years. Logistic regression found that PSA level (P=0.000) at diagnosis and patient's nodal-stage (P=0.02) were the only two independent variables able to predict the probability of bone metastasis among the newly diagnosed prostate cancer patients. Among thowse with a low PSA level less than 20ng/ml, and less than 10ng/ml, bone metastasis were detected in 10.3% (12 out of 117) and 9.7% (7 out of 72), respectively. However, by combining PSA level of 10ng/ml or lower, and nodal negative as the two criteria to predict negative bone scan, a relatively high negative predictive value of 93.8% was obtained. The probability of bone metastasis in prostate cancer can be calculated with this formula: -1.069+0.007(PSA value, ng/ml)+1.021(Nodal status, 0 or 1)=x Probability of bone metastasis=$2.718^x/1+2.718^x$. Conclusion: Newly diagnosed prostate cancer patients with a PSA level of 10ng/ml or lower and negative nodes have a very low risk of bone metastasis (negative predictive value 93.8%) and therefore bone scans may not be necessary.

Ureteral stricture formation after ureteroscope treatment of impacted calculi: A prospective study

Xeng Inn Fam,Praveen Singam,Christopher Chee Kong Ho,Radhika Sridharan,Rozita Hod,Badrulhisham Bahadzor,Eng Hong Goh,Guan Hee Tan,Zulkifli Zainuddin 대한비뇨의학회 2015 Investigative and Clinical Urology Vol.56 No.1

Purpose: Urinary calculi is a familiar disease. A well-known complication of endourological treatment for impacted ureteral stonesis the formation of ureteral strictures, which has been reported to occur in 14.2% to 24% of cases. Materials and Methods: This was a prospective study. Ureterotripsy treatment was used on patients with impacted ureteralstones. Then, after 3 months and 6 months, the condition of these patients was assessed by means of a kidney-ureter-bladder (KUB)ultrasound. If the KUB ultrasound indicated moderate to serious hydronephrosis, the patient was further assessed by means of acomputed tomography intravenous urogram or retrograde pyelogram to confirm the occurrence of ureteral strictures. Results: Of the 77 patients who participated in the study, 5 developed ureteral strictures. Thus, the stricture rate was 7.8%. Ananalysis of the intraoperative risk factors including perforation of the ureter, damage to the mucous membrane, and residual stoneimpacted within the ureter mucosa revealed that none of these factors contributed significantly to the formation of the uretericstrictures. The stone-related risk factors that were taken into consideration were stone size, stone impaction site, and duration ofimpaction. These stone factors also did not contribute significantly to the formation of the ureteral strictures. Conclusions: This prospective study failed to identify any predictable factors for ureteral stricture formation. It is proposed that allpatients undergo a simple postoperative KUB ultrasound screening 3 months after undergoing endoscopic treatment for impactedureteral stones.

Stratifying Patients with Haematuria into High or Low Risk Groups for Bladder Cancer: a Novel Clinical Scoring System

Tan, Guan Hee,Shah, Shamsul Azhar,Ann, Ho Sue,Hemdan, Siti Nurhafizah,Shen, Lim Chun,Abdul Galib, Nurudin Al-Fahmi,Singam, Praveen,Kong, Ho Chee Christopher,Hong, Goh Eng,Bahadzor, Badrulhisham,Zainud Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Haematuria is a common presentation of bladder cancer and requires a full urologic evaluation. This study aimed to develop a scoring system capable of stratifying patients with haematuria into high or low risk groups for having bladder cancer to help clinicians decide which patients need more urgent assessment. This cross-sectional study included all adult patients referred for haematuria and subsequently undergoing full urological evaluation in the years 2001 to 2011. Risk factors with strong association with bladder cancer in the study population were used to design the scoring system. Accuracy was determined by the area under the receiver operating characteristic (ROC) curve. A total of 325 patients with haematuria were included, out of which 70 (21.5%) were diagnosed to have bladder cancer. Significant risk factors associated with bladder cancer were male gender, a history of cigarette smoking and the presence of gross haematuria. A scoring system using 4 clinical parameters as variables was created. The scores ranged between 6 to 14, and a score of 10 and above indicated high risk for having bladder cancer. It was found to have good accuracy with an area under the ROC curve of 80.4%, while the sensitivity and specificity were 90.0% and 55.7%, respectively. The scoring system designed in this study has the potential to help clinicians stratify patients who present with haematuria into high or low r isk for having bladder cancer. This will enable high-risk patients to undergo urologic assessment earlier.

Incorporation of Smooth Muscle Cells Derived from Human Adipose Stem Cells on Poly(Lactic-co-Glycolic Acid) Scaffold for the Reconstruction of Subtotally Resected Urinary Bladder in Athymic Rats

Salem Salah Abood,Rashidbenam Zahra,Jasman Mohd Hafidzul,Ho Christopher Chee Kong,Sagap Ismail,Singh Rajesh,Yusof Mohd Reusmaazran,Md. Zainuddin Zulkifli,Haji Idrus Ruszymah Bt,Ng Min Hwei 한국조직공학과 재생의학회 2020 조직공학과 재생의학 Vol.17 No.4

Background: The urinary tract can be affected by both congenital abnormalities as well as acquired disorders, such as cancer, trauma, infection, inflammation, and iatrogenic injuries, all of which may lead to organ damage requiring eventual reconstruction. As a gold standard, gastrointestinal segment is used for urinary bladder reconstruction. However, one major problem is that while bladder tissue prevents reabsorption of specific solutes, gastrointestinal tissue actually absorbs them. Therefore, tissue engineering approach had been attempted to provide an alternative tissue graft for urinary bladder reconstruction. Methods: Human adipose-derived stem cells isolated from fat tissues were differentiated into smooth muscle cells and then seeded onto a triple-layered PLGA sheet to form a bladder construct. Adult athymic rats underwent subtotal urinary bladder resection and were divided into three treatment groups (n = 3): Group 1 (“sham”) underwent anastomosis of the remaining basal region, Group 2 underwent reconstruction with the cell-free scaffold, and Group 3 underwent reconstruction with the tissue-engineered bladder construct. Animals were monitored on a daily basis and euthanisation was performed whenever a decline in animal health was detected. Results: All animals in Groups 1, 2 and 3 survived for at least 7 days and were followed up to a maximum of 12 weeks post-operation. It was found that by Day 14, substantial ingrowth of smooth muscle and urothelial cells had occurred in Group 2 and 3. In the long-term follow up of group 3 (tissue-engineered bladder construct group), it was found that the urinary bladder wall was completely regenerated and bladder function was fully restored. Urodynamic and radiological evaluations of the reconstructed bladder showed a return to normal bladder volume and function.Histological analysis revealed the presence of three muscular layers and a urothelium similar to that of a normal bladder. Immunohistochemical staining using human-specific myocyte markers (myosin heavy chain and smoothelin) confirmed the incorporation of the seeded cells in the newly regenerated muscular layers. Conclusion: Implantation of PLGA construct seeded with smooth muscle cells derived from human adipose stem cells can lead to regeneration of the muscular layers and urothelial ingrowth, leading to formation of a completely functional urinary bladder.

Men’s Health Index: A Pragmatic Approach to Stratifying and Optimizing Men’s Health

Hui Meng Tan,Wei Phin Tan,Jun Hoe Wong,Christopher Chee Kong Ho,Chin Hai Teo,Chirk Jenn Ng 대한비뇨의학회 2014 Investigative and Clinical Urology Vol.55 No.11

Purpose: The proposed Men’s Health Index (MHI) aims to provide a practical and systematicframework for comprehensively assessing and stratifying older men with theintention of optimising their health and functional status. Materials and Methods: A literature search was conducted using PubMed from 1980to 2012. We specifically looked for instruments which: assess men’s health, frailty andfitness; predict life expectancy, mortality and morbidities. The instruments were assessedby the researchers who then agreed on the tools to be included in the MHI. Whenthere was disagreements, the researchers discussed and reached a consensus guidedby the principle that the MHI could be used in the primary care setting targetting menaged 55-65 years. Results: The instruments chosen include the Charlson’s Combined Comorbidity-AgeIndex; the International Index of Erectile Function-5; the International ProstateSymptom Score; the Androgen Deficiency in Aging Male; the Survey of Health, Ageingand Retirement in Europe Frailty Instrument; the Sitting-Rising Test; the SeniorFitness Test; the Fitness Assessment Score; and the Depression Anxiety StressScale-21. A pilot test on eight men was carried out and showed that the men’s healthindex is viable. Conclusions: The concept of assessing, stratifying, and optimizing men’s health shouldbe incorporated into routine health care, and this can be implemented by using the MHI. This index is particularly useful to primary care physicians who are in a strategic positionto engage men at the peri-retirement age in a conversation about their life goalsbased on their current and predicted health status.

Overview of Urethral Reconstruction by Tissue Engineering: Current Strategies, Clinical Status and Future Direction

Zahra Rashidbenam,Mohd Hafidzul Jasman,Pezhman Hafez,Guan Hee Tan,Eng Hong Goh,Xeng Inn Fam,Christopher Chee Kong Ho,Zulkifli Md Zainuddin,Reynu Rajan,Fatimah Mohd Nor,Mohamad Aznan Shuhaili,Nik Ritza 한국조직공학과 재생의학회 2019 조직공학과 재생의학 Vol.16 No.4

BACKGROUND: Urinary tract is subjected to a variety of disorders such as urethral stricture, which often develops as a result of scarring process. Urethral stricture can be treated by urethral dilation and urethrotomy; but in cases of long urethral strictures, substitution urethroplasty with genital skin and buccal mucosa grafts is the only option. However a number of complications such as infection as a result of hair growth in neo-urethra, and stone formation restrict the application of those grafts. Therefore, tissue engineering techniques recently emerged as an alternative approach, aiming to overcome those restrictions. The aim of this review is to provide a comprehensive coverage on the strategies employed and the translational status of urethral tissue engineering over the past years and to propose a combinatory strategy for the future of urethral tissue engineering. METHODS: Data collection was based on the key articles published in English language in years between 2006 and 2018 using the searching terms of urethral stricture and tissue engineering on PubMed database. RESULTS: Differentiation of mesenchymal stem cells into urothelial and smooth muscle cells to be used for urologic application does not offer any advantage over autologous urothelial and smooth muscle cells. Among studied scaffolds, synthetic scaffolds with proper porosity and mechanical strength is the best option to be used for urethral tissue engineering. CONCLUSION: Hypoxia-preconditioned mesenchymal stem cells in combination with autologous cells seeded on a prevascularized synthetic and biodegradable scaffold can be said to be the best combinatory strategy in engineering of human urethra.

Urethral strictures after bipolar transurethral resection of prostate may be linked to slow resection rate

Guan Hee Tan,Shamsul Azhar Shah,Nurayub Md Ali,Eng Hong Goh,Praveen Singam,Christopher Chee Kong Ho,Zulkifli Md Zainuddin 대한비뇨의학회 2017 Investigative and Clinical Urology Vol.58 No.3

Purpose: This study aimed to determine the urethral stricture (US) rate and identify clinical and surgical risk factors associated with US occurrence after transurethral resection of the prostate using the bipolar Gyrus PlasmaKinetic Tissue Management System (PK-TURP). Materials and Methods: This was an age-matched case-control study of US occurrence after PK-TURP. Retrospective data were collected from the hospital records of patients who had a minimum of 36 months of follow-up information. Among the data collected for analysis were prostate-specific antigen level, estimated prostate weight, the amount of prostate resected, operative time, history of urinary tract infection, previous transurethral resection of the prostate, and whether the PK-TURP was combined with other endourological procedures. The resection rate was calculated from the collected data. Univariate and multivariate analyses were performed to identify clinical and surgical risk factors related to US formation. Results: A total of 373 patients underwent PK-TURP between 2003 and 2009. There were 13 cases of US (3.5%), and most of them (10 of 13, 76.9%) presented within 24 months of surgery. Most of the US cases (11 of 13, 84.6%) occurred at the bulbar urethra. Multivariable logistic regression analyses identified slow resection rate as the only risk factor significantly associated with US occurrence. Conclusions: The US rate of 3.5% after PK-TURP in this study is comparable to contemporary series. A slow resection rate seems to be related to US occurrence. This should be confirmed by further studies; meanwhile, we must be mindful of this possibility when operating with the PK-TURP system.